RGD Reference Report - Fatty acids change the conformation of uncoupling protein 1 (UCP1). - Rat Genome Database

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Fatty acids change the conformation of uncoupling protein 1 (UCP1).

Authors: Divakaruni, AS  Humphrey, DM  Brand, MD 
Citation: Divakaruni AS, etal., J Biol Chem. 2012 Oct 26;287(44):36845-53. doi: 10.1074/jbc.M112.381780. Epub 2012 Sep 5.
RGD ID: 11541104
Pubmed: PMID:22952235   (View Abstract at PubMed)
PMCID: PMC3481287   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M112.381780   (Journal Full-text)

UCP1 catalyzes proton leak across the mitochondrial inner membrane to disengage substrate oxidation from ATP production. It is well established that UCP1 is activated by fatty acids and inhibited by purine nucleotides, but precisely how this regulation occurs remains unsettled. Although fatty acids can competitively overcome nucleotide inhibition in functional assays, fatty acids have little effect on purine nucleotide binding. Here, we present the first demonstration that fatty acids induce a conformational change in UCP1. Palmitate dramatically changed the binding kinetics of 2'/3'-O-(N-methylanthraniloyl)-GDP, a fluorescently labeled nucleotide analog, for UCP1. Furthermore, palmitate accelerated the rate of enzymatic proteolysis of UCP1. The altered kinetics of both processes indicate that fatty acids change the conformation of UCP1, reconciling the apparent discrepancy between existing functional and ligand binding data. Our results provide a framework for how fatty acids and nucleotides compete to regulate the activity of UCP1.

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Ucp1  (uncoupling protein 1)

Additional Information